Biomedical subjects

S M Flechner

Publications and source records attributed to S M Flechner.

At least 55 records · Page 3Linked to original sources

PubMed1987

Complications of cyclosporine-prednisone immunosuppression in 402 renal allograft recipients exclusively followed at a single center for from one to five years.

The therapeutic efficacy of cyclosporine (CsA) as an immunosuppressive agent was complemented by a modest, long-term incidence of toxic complications in 402 renal allograft recipients engrafted one to five years prior to analysis. The overall patient and graft survivals at one year were 97% and 84% (actual), and at five years 92% and 67% (actuarial). The immunosuppressive therapeutic index was excellent: only 12% of allografts were lost from rejection, with 5% of patients succumbing to infection. While infections were common, tending to emanate in the urinary tract or to be viral in etiology, they were generally mild and readily controlled. Only four patients displayed malignancies; none succumbed to this cause. The most common toxic complication was hypertrichosis, which was accentuated in pediatric patients. While tremors occurred in 20% of patients, primarily during the first three months, other neuroectodermal complications of parethesias, depression, somnolence, and seizures were rare. Hepatotoxicity, which was noted in 50% of patients, particularly recipients of cadaveric grafts, generally was first seen as a transaminase elevation, at least partially reversible by dose-reduction and abating by the third year. Associated disturbances of cholelithiasis and pancreatitis were occasionally observed. Nephrotoxicity was the only persistent, long-term complication. Hypertension occurred in 72% of patients during the first month, 36% in the second year, and about 15% thereafter. Hyperuricemia, which occurred in about 30% of recipients during the first two years, was occasionally associated with symptomatic gout. The mean serum creatinine level remained elevated throughout the follow-up period at 1.8-1.9 mg/dl, suggesting persistent, but nonprogressive, drug-induced renal injury. The present analysis documents the relative safety of CsA for long-term therapy, and highlights the need for new approaches to ameliorate drug-induced nephrotoxicity.

Adolescent↗

PubMed1987

Immunoregulatory mechanisms in cyclosporine-treated renal allograft recipients.

Cyclosporine (CsA)-treated recipients of a primary cadaveric (CAD) renal allograft were postoperatively evaluated for their donor and nonspecific immune responsiveness. Recipients with posttransplant (Tx) T helper (TH):T suppressor (TS) cell ratios less than 1.0 (averaged for the first 0-30 post-Tx days) had significantly better one-year serum creatinines (SCr) of 1.8 +/- 0.7 vs. 2.3 +/- 0.6 for recipients with TH:TS ratios greater than 1.0, P less than 0.05. Significantly fewer rejection episodes (30 vs. 57) and immune graft losses (10 vs. 19) were experienced by recipients with TH:TS ratios less than 1.0 vs. greater than 1.0, P less than 0.001 and 0.05, respectively. Recipients with TH:TS ratios less than 1.0 vs. greater than 1.0 displayed significantly lower post-Tx panel mixed lymphocyte culture (PMLC) stimulation indices (SI) of 24 +/- 11 vs. 38 +/- 6, P less than 0.05 and donor MLC SI of 15 +/- 6 vs. 31 +/- 8, P less than 0.05, respectively. Moreover, the post-Tx:pre-Tx donor MLC ratio of 0.58 +/- 0.2 vs. 1.1 +/- 0.32 was significantly lower in recipients with TH:TS ratios less than 1.0 vs. greater than 1.0, P less than 0.05. The suggested donor hyporesponsiveness in recipients with post-Tx TH:TS ratios less than 1.0 was further investigated by studying 46 CsA-treated allograft recipients for their ability to display regulatory T cell or adherent monocyte MLC suppressor activity. With a mean follow-up time of 5 +/- 4 months (range 0.5-14 months) we observed that 46% (21/46) of the patients displayed T cell suppressor activity, including 35% (16/46) with T-donor-specific and 46% (21/46) with T non-specific MLC suppressor activity. Additionally, 59% (27/46) of the patients also displayed nonspecific adherent monocyte MLC suppression. Recipients displaying either T cell or adherent monocyte suppression experienced significantly fewer rejection episodes than patients with no suppressor cell activity (P less than 0.05). Moreover, patients with T cell suppressor activity displayed a significantly lower panel and donor MLC vs. patients not displaying T suppressor activity (P less than 0.05. and 0.05, respectively). Finally, there was a significant correlation between the display of T cell suppressor activity in patients who were matched with their donors at the HLA-DR locus vs. no display of T suppressor activity in those patients unmatched with their donors at the HLA-DR locus.

Cyclosporins↗

PubMed1987

Investigation of HTLV-3 serology in a renal transplant population.

From June 1977 to March 1985, 572 renal transplants were performed at The University of Texas Medical School at Houston. This represented 220 patients (151 cadaveric [CAD] and 69 living-related donor [LRD] recipients) treated with azathioprine and prednisone (Aza-Pred) and 352 patients (250 CAD and 102 LRD) treated with cyclosporine (CsA) and Pred. Sera from each recipient before and after transplant (Tx) as well as from each of their 436 donors (265 CAD and 171 LRD) were retrospectively tested for the presence of antibody to the human T cell lymphotrophic virus type III (HTLV-3) by enzyme immunoassay (EIA) and Western Blot analysis. Of the 436 donors tested, only 1/265 (0.38%) CAD donors were both EIA repeatedly reactive and Western Blot positive, whereas none of the 171 LRD were reactive. Pre-Tx, 4/401 (1.0%) CAD and 1/171 (0.6%) LRD recipient sera were EIA repeatedly reactive, however, all 5 were to be Western Blot negative. Post-Tx, 4.2% of the sera (24/572, 4 LRD and 20 CAD recipients) were EIA-reactive. All 20 CAD recipient sera were subsequently found to be negative with Western Blot testing. However, 2 LRD sera (2/572, 0.35%) displayed EIA reactivity as well as Western Blot positivity. One LRD, Western-Blot-positive recipient is alive and well with a functioning allograft 39 months post-Tx, whereas the second LRD, Western Blot positive recipient died of septic complications 16 months post-Tx. Finally, the recipient of the Western-Blot-positive CAD allograft is alive with a well-functioning graft and remains EIA and Western-Blot-negative 36 months post-Tx.

Antibodies, Viral↗

PubMed1987

Exacerbation of cyclosporine toxicity by concomitant administration of erythromycin.

Cyclosporine (CsA), an immunosuppressive drug widely used in clinical organ transplantation, causes a variety of side effects, including parenchymal complications of nephrotoxicity and hepatotoxicity. Erythromycin ethinylsuccinate (EES), a macrolide antibiotic frequently administered to transplant patients afflicted with pneumonias caused by Mycoplasma pneumoniae and Legionella pneumophila, markedly potentiated parenchymal drug toxicity in nine (three renal and six cardiac) CsA-treated allograft recipients. The mean and median blood urea nitrogen (BUN), creatinine, and total bilirubin increased upon initiation of EES treatment: in the renal recipients from 27, 1.7, and 0.5 mg/dl, respectively, before, to a mean and median of 81/101, 8.3/3.9, and 2.1/1.2 mg/dl during, and to 72/22, 1.9/1.7, and 0.6/0.5 mg/dl after cessation of EES treatment. The median serum radioimmunoassay (RIA)-determined CsA trough value of 147 ng/ml prior, rose to a zenith of 1125 ng/ml during, EES therapy. In the six cardiac recipients, the mean and median BUN, creatinine, and total bilirubin of 51/45, 1.5/1.3, 1.2/1.3 mg/dl, respectively, before, rose to 100/91, 3.7/3.6, and 2.3/2.1 mg/dl during, and fell to 49/44, 1.8/2.1, and 1.0/0.8 mg/dl after, cessation of EES. The mean serum CsA trough value of 185 ng/ml rose to 815 ng/ml during EES administration. Since EES and CsA are both metabolized by the hepatic cytochrome P450 mixed-function oxidase system, simultaneous use of these two drugs may decrease CsA metabolism, with consequent elevation of blood levels and induction of CsA toxicity. Therefore, blood level monitoring and careful regulation of CsA dose are necessary, in order to achieve the safe use of EES in transplant recipients.

Bilirubin↗

PubMed1987